The long-term objective is to determine the role of prostaglandins in the pathogenesis of hypertension. We plan to measure urinary excretion of PGE2, 6-keto-PGF1 and PGF2 in patients with various forms of hypertension to determine if a deficiency of prostaglandin excretion and presumably renal production is present and whether the abnormality involves more than one prostaglandin. In view of the fact that prostaglandins are involved in several aspects of renal function, we will compare renal function in the low excreters and normal excreters of prostaglandins. We will study renal plasma flow, creatinine clearance, sensitivity to vasopressin, and ability to excrete a sodium load and plasma renin activity. The role of prostaglandins in glucocorticoid hypertension will be studied. Glucocorticoids will be administered to normal humans and urinary and plasma prostaglandins measured. In animals, vascular tissue production of prostaglandins in vitro will be measured as well. Similar in vitro studies of vascular tissue production of prostaglandins in experimental models of genetic hypertension will be carried out. Prostaglandin production by vascular rings and endothelial and smooth muscle cell cultures will be analyzed. The role of prostaglandins in the blood pressure lowering effect of several anti-hypertensive agents will be investigated. We will measure urinary and plasma prostaglandin levels in response to acute and chronic therapy in humans and will evaluate the effect of these antihypertensive agents on human endothelial and smooth muscle cells in vitro. Prostaglandins are implicated in the control of renin secretion. The mechanism by which prostaglandins stimulate renin will be investigated in vitro using rat slices and isolated glomeruli. The relationship between prostaglandins, calcium and cyclic AMP will be studied.